Department of Economics and Business Economics

Association of Alzheimer Disease With Life Expectancy in People With Down Syndrome

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Maria Florencia Iulita, Biomedical Research Institute Sant Pau
  • ,
  • Diana Garzón Chavez, Biomedical Research Institute Sant Pau
  • ,
  • Maria Klitgaard Christensen
  • ,
  • Natalia Valle Tamayo, Biomedical Research Institute Sant Pau
  • ,
  • Oleguer Plana-Ripoll
  • Sonja A Rasmussen, University of Florida College of Medicine
  • ,
  • Marta Roqué Figuls, Biomedical Research Institute Sant Pau
  • ,
  • Daniel Alcolea, Biomedical Research Institute Sant Pau
  • ,
  • Laura Videla, Biomedical Research Institute Sant Pau
  • ,
  • Isabel Barroeta, Biomedical Research Institute Sant Pau
  • ,
  • Bessy Benejam, Biomedical Research Institute Sant Pau
  • ,
  • Miren Altuna, Biomedical Research Institute Sant Pau
  • ,
  • Concepción Padilla, Biomedical Research Institute Sant Pau
  • ,
  • Jordi Pegueroles, Biomedical Research Institute Sant Pau
  • ,
  • Olivia Belbin, Biomedical Research Institute Sant Pau
  • ,
  • María Carmona-Iragui, Biomedical Research Institute Sant Pau
  • ,
  • Rafael Blesa, Biomedical Research Institute Sant Pau
  • ,
  • Alberto Lleó, Biomedical Research Institute Sant Pau
  • ,
  • Alexandre Bejanin, Biomedical Research Institute Sant Pau
  • ,
  • Juan Fortea, Biomedical Research Institute Sant Pau, Barcelona Down Medical Center

Importance: People with Down syndrome have a high risk of developing Alzheimer disease dementia. However, penetrance and age at onset are considered variable, and the association of this disease with life expectancy remains unclear because of underreporting in death certificates.

Objective: To assess whether the variability in symptom onset of Alzheimer disease in Down syndrome is similar to autosomal dominant Alzheimer disease and to assess its association with mortality.

Design, Setting, and Participants: This study combines a meta-analysis with the assessment of mortality data from US death certificates (n = 77 347 case records with a International Classification of Diseases code for Down syndrome between 1968 to 2019; 37 900 [49%] female) and from a longitudinal cohort study (n = 889 individuals; 46% female; 3.2 [2.1] years of follow-up) from the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI).

Main Outcomes and Measures: A meta-analysis was conducted to investigate the age at onset, age at death, and duration of Alzheimer disease dementia in Down syndrome. PubMed/Medline, Embase, Web of Science, and CINAHL were searched for research reports, and OpenGray was used for gray literature. Studies with data about the age at onset or diagnosis, age at death, and disease duration were included. Pooled estimates with corresponding 95% CIs were calculated using random-effects meta-analysis. The variability in disease onset was compared with that of autosomal dominant Alzheimer disease. Based on these estimates, a hypothetical distribution of age at death was constructed, assuming fully penetrant Alzheimer disease. These results were compared with real-world mortality data.

Results: In this meta-analysis, the estimate of age at onset was 53.8 years (95% CI, 53.1-54.5 years; n = 2695); the estimate of age at death, 58.4 years (95% CI, 57.2-59.7 years; n = 324); and the estimate of disease duration, 4.6 years (95% CI, 3.7-5.5 years; n = 226). Coefficients of variation and 95% prediction intervals of age at onset were comparable with those reported in autosomal dominant Alzheimer disease. US mortality data revealed an increase in life expectancy in Down syndrome (median [IQR], 1 [0.3-16] years in 1968 to 57 [49-61] years in 2019), but with clear ceiling effects in the highest percentiles of age at death in the last decades (90th percentile: 1990, age 63 years; 2019, age 65 years). The mortality data matched the limits projected by a distribution assuming fully penetrant Alzheimer disease in up to 80% of deaths (corresponding to the highest percentiles). This contrasts with dementia mentioned in 30% of death certificates but is in agreement with the mortality data in DABNI (78.9%). Important racial disparities persisted in 2019, being more pronounced in the lower percentiles (10th percentile: Black individuals, 1 year; White individuals, 30 years) than in the higher percentiles (90th percentile: Black individuals, 64 years; White individuals, 66 years).

Conclusions and Relevance: These findings suggest that the mortality data and the consistent age at onset were compatible with fully penetrant Alzheimer disease. Lifespan in persons with Down syndrome will not increase until disease-modifying treatments for Alzheimer disease are available.

Original languageEnglish
Article numbere2212910
JournalJAMA Network Open
Volume5
Issue5
Pages (from-to)e2212910
Number of pages15
ISSN2574-3805
DOIs
Publication statusPublished - 2 May 2022

Bibliographical note

Publisher Copyright:
© 2022 BMJ Publishing Group. All rights reserved.

    Research areas

  • Aged, Alzheimer Disease/complications, Cohort Studies, Down Syndrome/complications, Female, Humans, Life Expectancy, Longitudinal Studies, Male, Middle Aged

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